Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a rare autosomal recessive neuromuscular disorder. Argov, et al., Neurology 60, 1519-1523 (2003); Eisenberg, et al. (2001) Nat Genet 29, 83-87 (2001); Griggs, et al. (1995) Ann Neurol 38, 705-713 (1995). The disease usually manifests at approximately 20 years of age with foot drop and slowly progressive muscle weakness and atrophy. Histologically, it is associated with muscle fiber degeneration and formation of vacuoles containing 15-18 nm tubulofilaments that immunoreact like β-amyloid, ubiquitin, prion protein and other amyloid-related proteins. Askanas et al. Curr Opin Rheumatol 10, 530-542 (1998); Nishino, et al. (2005) Acta Myol 24, 80-83 (2005); Askanas, et al. Ann Neurol 34, 551-560 (1993); Argov, et al. Curr Opin Rheumatol 10, 543-547 (1998). Both weakness and histological changes initially spare the quadriceps. However, the disease is relentlessly progressive, with patients becoming incapacitated and wheelchair-confined within two to three decades. There is no treatment available.
Accordingly, new compositions and methods are needed for treating hereditary inclusion body myopathy and related diseases.